The initiation of the herpes simplex virus lytic replication cycle depends upon the coordinated expression of the viral (IE) immediate early genes. These genes are controlled by a complex multiprotein enhancer assembly that consists of viral and cellular components. Studies of the various components, protein interactions, viral and cellular functions provides both a model for cellular transcriptional regulation as well as insights into the mechanisms utilized by the virus. The focus of the laboratory is the identification and characterization of the critical components of this regulatory pathway. The mammalian C1 factor (HCF-1) is one of the more complex factors involved in both the assembly of the enhancer complex and the activation of the IE genes. Studies focus upon both it?s functions during the viral lytic cycle as well as in the normal cellular processes. The importance of both is underscored by the complex viral-cell interactions that impact the lytic and latent states of the viral life cycle. These studies (i) have delineated functional domains of the protein; (ii) identified both cellular and viral proteins that interact with various domains; (iii) elucidated a novel mechanism of HCF-1 mediated regulation of HSV DNA replication; (iv) characterized a unique mechanism for the regulation of protein-protein interactions via site-specific proteolytic processing; (iv) identified the protein as the essential component of the viral IE gene expression; and (v) identified cellular genes regulated by the protein using a genetic system that specifically sequesters the factor.